There has been increasing attention directed to the potential benefits of moderate drinking, particularly in middle-aged to older adults. Importantly, most of this work has focused on moderate drinking as a lifestyle, without direct consideration of the acute effects of moderate doses of alcohol on older drinkers (i.e., moderate drinking as an event). Little is known about the effects of moderate doses of acute alcohol on neurocognitive, neurophysiological and performance measures among healthy adults in middle to later adulthood. From a scientific perspective, the absence of these data restrains conclusions regarding the direct effects of alcohol on behavior as well as the compensatory neurobehavioral mechanisms that may impact outcome. From a clinical perspective, the absence of data greatly restrains recommendations regarding the short-term risks associated with bouts of moderate drinking for a growing segment of the population. Pilot work (partial support, NIAAA R03AA14039, Nixon, principal investigator) revealed age effects suggesting that a low dose of alcohol negatively affected performance on the ascending limb to a greater extent than on the descending limb, but only for older (as opposed to younger) participants/subjects (Ss). Interestingly, the older group was also less aware of their deficits. Importantly, age-related differences in pharmacokinetics could not account for these results [40]. Interestingly, visual attention assessed at peak breath alcohol concentration (~.04 percent) was impaired equally for older Ss who received alcohol and those who actually received placebo but believed they had received alcohol [39] [See Section 3]. Unfortunately, representation across the conditions was not sufficient to allow gender- related analyses. These data provide conceptual guidance and reinforce the feasibility of and need for a systematic study that includes a greater dose range, larger samples for gender analyses, and more comprehensive neurobehavioral assessments. Therefore, we propose a double-blind placebo controlled study using a 2 (age: younger (25-35)/older (55-70)) by 2 (gender) by 3 (placebo, low (~.04 percent), and moderate (~. 065 percent)) alcohol dose factorial design to clarify the main and interactive effects of these variables on psychomotor speed, set-shifting abilities, attentional processes, and complex integrated behavior (i.e., driving simulation). To enhance the theoretical import of the work, we bring current models of cognitive aging to bear. The study has significant relevance to basic and applied studies of moderate (i.e., legal) levels of acute alcohol, healthy aging and cognition, and gender differences in sensitivity to the neurobehavioral effects of alcohol administration. PUBLIC HEALTH RELEVANCE: There has been increasing attention to potential cardiovascular and quality of life benefits associated with a moderate drinking lifestyle, particularly in middle aged to older adults. However, little systematic work has focused on the acute effects of these moderate doses on cognitive and performance variables critical to effective higher order functions including decision-making and tracking information. Building on our pilot work, this project compares performance between male and female older and younger moderate drinkers under 3 alcohol conditions designed to achieve zero blood alcohol concentration (placebo (0), a low level (~.04 percent) or a moderate level (~ .065 percent) to examine 1) to what extent and under what low-to-moderate alcohol doses older adults may demonstrate differential sensitivity and 2) whether older drinkers can accurately anticipate alcohol- related deficits. The findings will not only allow us to disentangle age from alcohol effects on neurocognitive tasks, but also shed light on differential risk for injury and negative outcome associated with episodes of moderate drinking among non-problem, older drinkers.